This project involves three primary lines of research to gain insights into the effects of sex steroid hormones on cognitive function: 1) sex differences in cognitive function; 2) changes in cognition in relation to natural fluctuations in endogenous hormones; and 3) changes in cognition associated with exogenous hormone intervention. Studies of sex differences in cognitive function provide indirect support for hormonal modulation of cognitive function and point to cognitive domains that might be particularly sensitive to the effects of sex steroid hormones. Studies of changes in cognition across the menstrual cycle indicate that fluctuations in estrogen are associated with fluctuations in performance on cognitive tests on which women typically show an advantage. Studies of changes in cognition in association with the use of hormone replacement therapy (HRT) suggested a lower risk of Alzheimer's disease among women receiving HRT. A recent study suggested a selective beneficial effect of HRT on memory, particularly verbal memory, among healthy older women receiving HRT. This pattern of results is notable in light of the female advantage on tests of verbal memory. However, there is little evidence that HRT influences performance on other cognitive tasks on which women show a comparative advantage over men. This suggests that the effects of hormones on cognition may be age-specific. Neuroimaging studies provide insights into the neural underpinnings of hormone effects on cognitive performance. Hormone therapy is associated with changes in patterns of brain activation during performance of verbal and figural tasks and with increased blood flow to the hippocampus over time. These findings increase the biological plausibility that estrogen might help to prevent age-associated declines in cognition. Randomized clinical trials are needed to confirm this relationship and are underway. If estrogen may help to protect against cognitive decline, then medications that block estrogen in some body tissues might increase the risk for cognitive decline. CO-STAR is a recently initiated study of longitudinal change in cognition in 1800 women receiving such medications. These studies may provide critical information for women and their physicians about how commonly used medications might effect cognitive function.